The αvβ6 integrin induces gelatinase B secretion in colon cancer cells

Abstract

In human cancers, the co-operative role between cell-adhesion receptors and proteases capable of degrading matrix barriers remains poorly understood. We have previously reported that the epithelium-restricted integrin αvβ6 becomes highly expressed in colon cancer compared with normal mucosa and that heterologous expression of αvβ6 in colon cancer cells is associated with enhanced cell growth. Herein, we report that: αvβ6 expression in colon cancer cells leads to a relative increase in secretion of the matrix metalloproteinase gelatinase B over its respective inhibitor and that this secretion parallels the level of cell-surface β6 expression. The αvβ6- mediated gelatinase B secretion is associated with increased proteolysis of denatured collagen at the cell surface, and inactivation of gelatinase B in β6-expressing tumour cells inhibits cell spreading and proliferation within 3-dimensional collagen matrices. Our findings suggest that αvβ6-mediated gelatinase B secretion is important in the progression of human colon cancer.